Başkent Üniversitesi Yayınları
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Item Cytokine Gene Polymorphisms in Renal Transplant Recipients(Başkent Üniversitesi, 2006-12) Azarpira, N.; Aghdaie, MH.; Geramizadeh, B.; Behzadi, S.; Nikeghbalian, S.; Sagheb, F.; Rahsaz, M.; Behzad-Behbahanie, A.; Ayatollahi, M.; Darai, M.; Azarpira, MR.; Banihashemie, M.; Tabei, SZ.Objective: Acute rejection remains an important cause of graft loss after renal transplantation, and cytokines are key mediators in the induction and effector phases of all immune and inflammatory responses. However, the influence of gene polymorphisms on the functional immune response of transplant recipient outcomes remains controversial. Materials and Methods: The amplification refractory mutation system polymerase chain reaction was used to detect the interleukin-10 (IL-10) (-1082 G/A), tumor necrosis factor-alpha (TNF-α) (-308 G/A), and interferon-gamma (IFN-γ) (+874 T/A) single nucleotide polymorphisms in 100 of the first adult kidney recipients at our institution who were receiving cyclosporine-based immunosuppressive therapy. The diagnosis of acute rejection was based on clinical and histologic findings according to the Banff criteria. Results: The results of multivariate analyses showed no significant association between episodes of acute rejection and single nucleotide polymorphisms in IL-10, TNF-α genes, or dinucleotide repeat polymorphisms in the IFN-γ gene. Conclusions: Our results demonstrate that cytokine gene polymorphisms did not influence the early outcome of kidney transplantation.Item Plasmapheresis in the Treatment of Early Acute Kidney Allograft Dysfunction(Başkent Üniversitesi, 2006-12) Nafar, Mohsen; Farrokhi, Farhat; Hemati, Keyvan; Pour-Reza-Gholi, Fatemeh; Firoozan, Ahmad; Einollahi, BehzadObjective: To evaluate the efficacy of plasmapheresis (PP) in kidney transplant recipients with acute humoral rejection (AHR). Patients and Methods: A retrospective review was conducted of all kidney allograft recipients who had undergone PP rescue therapy for early acute allograft dysfunction diagnosed as AHR at Shaheed Labbafinejad Medical Center from 1995 to 2002. Results: Twelve patients (4 men and 8 women; median age, 32 years; age range, 15-68 years) with AHR were treated with PP. The median time from transplantation to AHR was 6 days (range, 2-7 days). PP was performed in 2 to 11 sessions (median, 8.5 sessions) in the patients studied. Eight patients responded to that treatment, and their creatinine value normalized. Those responders were monitored for a median of 162.5 weeks (range, 69.3-484.7 weeks), and all had a functioning allograft during the follow-up period except for 1 patient in whom the graft failed 154 weeks after transplantation. In the 4 remaining patients (nonresponders), the allograft failed within the first posttransplant month. The median time from the acute serum creatinine elevation to the initiation of PP was 6 days in responders and 18.6 days in nonresponders (P = .37). Conclusions: We suggest that PP with or without other therapeutic measures may have a role in the salvage of grafts with early acute dysfunction that is resistant to conventional therapy. Our findings indicate that graft survival in patients with AHR who respond to PP can be comparable to that in other kidney recipients.Item Urologic Complication Rates in Kidney Transplantation after a Novel Ureteral Reimplantation Technique(Başkent Üniversitesi, 2006-12) Haberal, Mehmet; Karakayali, Hamdi; Sevmis, Sinasi; Moray, Gokhan; Arslan, GulnazOur transplantation team has performed 1615 renal transplantations since 1975. After September 2003, we began a corner-saving technique for urinary tract continuity. In this study, we analyzed these 174 renal transplantations retrospectively. The mean recipient age was 31.6 years (range, 7 to 66). The mean donor age was 39.8 years (range, 6 to 67). For ureteral reimplantation, a running suture is started 3 mm ahead of the middle of the posterior wall and is finished 3 mm afterward. After the last stitch, both ends of the suture material are pulled, and the posterior wall of the ureter and bladder are approximated tightly. The anterior wall is sewn either with the same suture or another running suture. Since using this technique, we have not employed a double-J or any other stent to prevent ureteral complications at the anastomosis site. We have seen only 4 (2.2%) ureteral complications (2 ureteral stenosis and 2 anastomotic leaks) during a follow-up period of 18.9 months. In conclusion, due to the low complication rate, we believe that our new technique is the safest way to perform a ureteroneocystostomy.Item Ethical Issues in Living Donor Kidney Transplantation(Başkent Üniversitesi, 2006-12) Mazaris, Evangelos; Papalois, Vassilios E.The ethical issues of living donor kidney transplantation, which is the treatment of choice for patients with end-stage renal failure, are the focus of intense debate. Some of those issues are related to the safety of the operation for the donor, and others are related to the motivation of the donor, the approach to and evaluation of the donor, donation by strangers, the commercialization of donation, surrogate consent for donation, and the acceptance of minors as donors. The lack of clear consensus regarding these issues results in differences in practice, not only among countries but also among transplant centers. We believe that after an open debate, agreement on certain generally accepted principles can be achieved. Such an agreement would protect potential donors and recipients and would ensure the future of living donor kidney transplantation.Item Cytomegalovirus Disease with Atypical Presentation in a Renal Transplant Patient: Case Report(Başkent Üniversitesi, 2006-06) Khosravi, Masoud; Nobakht, Ali; Nikokar, Abdolah R.Infection is a major problem after kidney transplantation. Cytomegalovirus (CMV) is the most common viral infection affecting transplant patients. This report presents a rare clinical manifestation of CMV in the form of a hemorrhoid in a 58-year-old woman. One week after undergoing an external hemorrhoidectomy, the patient presented with fever, leukopenia, and thrombocytopenia. Pathological analysis showed CMV in the hemorrhoidal tissue, which was confirmed via a positive PP65 antigenemia assay. Therapy with ganciclovir (250 mg IV b.i.d. for 2 weeks) was started. The patient’s response to treatment was good, and she has been doing well since that time. Her plasma creatinine level 2 years later was 79.2 µmol/L (normal range, 53-106 µmol/L). Physicians must always be aware of the hazards of CMV in immunocompromised patients with typical, and even with atypical, presentations. Taking into consideration the statement, “prophylaxis precedes treatment,” nephrologists must try to detect CMV in their patients (especially during the first 6 months after transplantation) prior to the appearance of any clinical manifestations. If CMV is detected, pre-emptive therapy with ganciclovir should be started.Item Ischemic Training and Immunosuppressive Agents Reduce the Intensity of Ischemic Reperfusion Injury after Kidney Transplantation(Başkent Üniversitesi, 2006-06) Treska, Vladislav; Molacek, Jiri; Kobr, Jiri; Racek, Jaroslav; Trefil, Ladislav; Hes, OndrejObjectives: Ischemia-reperfusion injury affects posttransplant renal function, directly increases the probability of acute rejection, and is associated with chronic rejection and impaired long-term function. Animal studies suggest that ischemic preconditioning enhances resistance to ischemia and may be augmented by treating donors using immunosuppressant agents. This study sought to confirm the hypothesis that a combination of ischemic training and immunosuppression prior to renal harvest would maximize a transplanted kidney’s resistance to ischemia-reperfusion injury. Materials and Methods: Landrace pigs underwent either preharvest immunosuppression plus left kidney ischemic training (group 1, n = 6) or ischemic training alone (group 2, n = 6). Immunosuppression was composed of mycophenolate mofetil (20 mg/kg) and tacrolimus (0.1 mg/kg) administered intravenously 30 minutes before training. Training comprised 2 cycles of left renal pedicle occlusion for 5 minutes followed by release (reperfusion) for 10 minutes. Warm renal ischemia was then induced by clamping the left renal pedicle for 30 minutes, followed by heterotopic left kidney transplantation. Blood from the transplanted kidney renal vein was sampled directly at 0, 10, 20, 40, and 60 minutes posttransplantation for malondialdehyde (a reactive oxygen species marker), tumor necrosis factor-alpha (TNFα), interleukins 6 and 8 (inflammatory cytokines), and erythrocyte-reduced glutathione (an antioxidant). Renal histology was graded on a 3-point scale. Results: Reperfusion levels of malondialdehyde, TNFα, and interleukin 6 were significantly lower in group 1 at both 40 and 60 minutes. None of the animals in group 1 (0/6) that received preharvest immunosuppression showed severe interstitial inflammation, compared with 4 of 6 animals in group 2 that did (P < .03). Conclusions: Preharvest immunosuppression with mycophenolate mofetil and tacrolimus significantly decreases immediate posttransplant reactive oxygen species and inflammatory cytokine production, enhances the protective effect of ischemic training, and should not only reduce ischemia-reperfusion injury in transplanted kidneys but also should enhance immediate and long-term graft function while preventing acute rejection.Item Association between Cyclosporine Concentration and Genetic Polymorphisms of CYP3A5 and MDR1 during the Early Stage after Renal Transplantation(Başkent Üniversitesi, 2006-06) Azarpira, N.; Aghdaie, MH.; Behzad-Behbahanie, A.; Geramizadeh, B.; Behzadi, S.; Malekhoseinie, SA .; Raisjalal, GH.; Rahsaz, M.; Pourgholami, A.; Sagheb, F.Objectives: Cyclosporine (CsA) has a narrow therapeutic range, and its pharmacokinetic characteristics vary among individuals. It also is a substrate for cytochrome P450 (CYP) 3A and P-glycoprotein, the product of the multidrug resistance 1 (MDR1) and CYP3A5 genes. Some of the single nucleotide polymorphisms (SNPs) in these genes are associated with deficient protein expression and reduced in vivo activity. We postulated that in renal transplant recipients, these SNPs should be associated with interindividual variations in CsA pharmacokinetics. Materials and Methods: In 88 Iranian renal transplant patients receiving CsA, CYP3A5 and MDR1 genotypes were determined by polymerase chain reaction, followed by restriction fragment length polymorphism analysis. Whole blood trough CsA concentrations were measured by radioactive immunosorbent assay. The dose-adjusted concentration (ng/mL per mg/kg/d) was calculated at 1 day (± 2 days), 7 days, and 1 month after transplantation. Results: The MDR-1 wild-type genotype (3435CC) was observed in 17 patients (19%), whereas 45 patients (51%) were heterozygous (3435CT), and 26 patients (30%) were homozygous (3435 TT) for the mutation. In the days immediately after transplantation, we found a correlation between the concentration/dose ratio and the exon 26 MDR single nucleotide polymorphisms (33.3 ± 15.24 µg mg/L/kg in the CT group vs 44.1 ± 28.4 µg mg/L/kg in the TT group, P = .019). This ratio was significantly higher in subjects homozygous for the mutation (3435TT). This significant difference was not seen 1 week or 1 month after transplantation. All patients had the CYP3A5*3/*3 genotype, so no differences among the CYP3A5*1/*3 genotypes were found. Conclusions: MDR-1 (3435CC) polymorphisms are associated with CsA pharmacokinetics and dose requirements in the first few days after renal transplantation. Pharmacogenetic methods could be used to help select the initial dosage and individualize immunosuppressive therapy. According to our results, the major genotype of our recipients is CYP3A5*3/*3. According to the literature, the recommended starting dosage of CsA is 9-14 mg/kg/day; however, the Iranian population has a good response with lower dosages (3-5 mg/kg/day), which may be explained by genetic differences.Item Lessons Learned from ABO-Incompatible Living Donor Kidney Transplantation : 20 Years Later(Başkent Üniversitesi, 2004-06) Squifflet, Jean-Paul; Meyer, Martine De; Malaise, Jacques; Latinne, Dominique; Pirson, Yves; Alexandre, Guy P JFrom June 1982 to November 1989, 39 ABO-incom-patible living kidney transplants were performed in 38 recipients. Pretransplant therapies included platelets donor transfusion (21/39), 2 to 5 plasmapheresis sessions (39/39), cyclosporin A with or without azathioprine (33/39) along with poly-clonal Abs (36/39) and splenectomy at the time of transplantation (37/39). The last patient who received 2 ABO-incompatible transplants was previously splenectomized (end-stage renal failure due to a cortical necrosis following a traumatic spleen rupture). Three other patients who did not undergo a splenectomy at the time of transplantation were not included in that series but hyperacutely rejected their transplants during the first postoperative week. The 31 ABO-incompatible living related donor graft recipients are alive. Graft loss occurred from acute and/or hyperacute rejection in 5 cases (none below 15 years of age) and from chronic rejection in 8 cases. By contrast, among the 8 ABO-incompatible living unrelated donor graft recipients, only one renal graft is still functioning 20 years later. Graft survival rates are better in the group of patients < 15 years (100%, 89%, 78%, and 78% at 2, 5, 10, and 15 years respectively) compared with the group > 15 years (77%, 77%, 64%, and 59% respectively; NS). Today, 20 years later, prospective randomized studies testing different steps in the preparation protocol are still lacking. Plasmaphereses were replaced by double filtration plasmapheresis and immunoadsorption. Splenectomy seems to be a prerequisite for successful ABO-incompatible living kidney transplantation but IV Ig globulins and rituximab are currently being successfully used without splenectomy along with the new immunosuppressive drugs. As the procedure remains unchanged, it might be reserved to patients where cadaver graft could not be a valuable alternative, especially for recipients < 15 years of age with a living related ABO-incompatible donor.Item ABO Incompatible Kidney Transplantation -Immunological Aspect-(Başkent Üniversitesi, 2003-12) Aikawa, Atsushi; Yamashita, Mioko; Hadano, Tomomi; Ohara, Takehiro; Arai, Kenji; Kawamura, Takeshi; Hasegawa, AkiraABO incompatible kidney transplantation (ABOINCKT) has been developed in Japan because of the shortage of cadaveric donors. We have performed 76 living-donor ABOINCKT in our center. Donor blood type antibody was removed by immunoadsorption or plasmapheresis and exchange. Immunosuppression consisted of cyclosporine or tacrolimus, steroid, and cyclophosphamide or azathioprine or mycophenolate mofetil and, recently, basiliximab. Splenectomy was routinely performed during the transplantation surgery. Donor blood type antigen was strongly expressed on the vascular endothelium at all time points and in all conditions posttransplantation. Red blood cell agglutination reaction (RBAR) was positive only in renal tissues from a patient with delayed hyperacute rejection. Donor specific antibody suppression was observed in 18 ABOINCKT recipients with blood type O from a donor with blood type A1 or B. ADCC activity was detected after pre-treatment. Acute humoral rejection in ABOINCKT can result from ADCC, as well as by antigen-antibody reaction. Five year graft and patient survival rates were 75% and 64% in 37 ABOINCKT recipients from June 1989 through December 1996, however they have been 100% in 39 ABOINCKT recipients since January 1997. Accommodation has been produced in ABOINCKT with the co-existence of blood type antigen and antibody. Currently, ABOINCKT is an alternative which should be considered, particularly for blood type O patients with extended waits for cadaveric transplantation and for pediatric patients.Item Infection Related Renal Impairment: A Major Cause of Acute Allograft Dysfunction(Başkent Üniversitesi, 2003-06) Nampoory, Mangalathillam R.N.; Johny, Kaivilayil V.; Costandy, Jamal N.; Nair, Madhavan P.; Said, Tarek; Homoud, Hani; Al-Muzairai, Ibrahim; Samhan, Mohmoud; Al-Moussawi, MustafaWe prospectively analyzed the impact of post transplant infections on the renal function in 532 stable renal transplant recipients (M=340; F=192) over a period of 5 years. Their age ranged from 3-75 years (40 + 14 years). During the follow-up period, 52 patients expired and 64 lost on follow-up. We defined renal impairment (RI) as a persistent rise in serum creatinine above 20% from baseline value. 495 episodes of RI occurred in 269 recipients. This included 180-36% episodes of acute rejection, 53-10.7% Cyclosporine toxicity, 236-47.7% infection related renal impairment [IRRI] and 26-5.3% others. The severity of renal failure is less in IRRI (100 + 90.2) than that of acute rejection (166 + 127.1), but was more than that in cyclosporine toxicity (50 + 42.2) . Sites of infection in IRRI were urinary (33%), respiratory (26.3%), septicemia (15.7%) and others (25.4%). Episode of IRRI occurred more frequently in LURD (159-67.4%) compared to LRD-RTR (50-21.2%). Occurrence of IRRI is more significantly higher in patients on triple drug immunosuppression (IS) (34.3%) than those on two drug IS (13.2%) (P=<0.01). Ecoli (23.1%), Pseudomonas (11.1%), Salmonella (8.8%), Klebsiella (8.8%) and Staphylococai (8.3%) were the major organisms producing IRRI. IRRI is frequent (27.8%) during the first six months. Present study denotes that IRRI is a major cause of acute failure in RTR.